Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis

Shu Yi Yin, Feng Yin Jian, Yung Hsiang Chen, Shih Chang Chien, Mao Chih Hsieh, Pei Wen Hsiao, Wen Hwa Lee, Yueh Hsiung Kuo, Ning Sun Yang

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17 Citations (Scopus)

Abstract

Tumour-associated fibroblasts (TAFs), as a functionally supportive microenvironment, play an essential role in tumour progression. Here we investigate the role of IL-25, an endogenous anticancer factor secreted from TAFs, in suppression of mouse 4T1 mammary tumour metastasis. We show that a synthetic dihydrobenzofuran lignan (Q2-3), the dimerization product of plant caffeic acid methyl ester, suppresses 4T1 metastasis by increasing fibroblastic IL-25 activity. The secretion of IL-25 from treated human or mouse fibroblasts is enhanced in vitro, and this activity confers a strong suppressive effect on growth activity of test carcinoma cells. Subsequent in vivo experiments showed that the anti-metastatic effects of Q2-3 on 4T1 and human MDA-MD-231 tumour cells are additive when employed in combination with the clinically used drug, docetaxel. Altogether, our findings reveal that the release of IL-25 from TAFs may serve as a check point for control of mammary tumour metastasis and that phytochemical Q2-3 can efficiently promote such anticancer activities.

Original languageEnglish
Article number11311
JournalNature Communications
Volume7
DOIs
Publication statusPublished - Apr 18 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    Yin, S. Y., Jian, F. Y., Chen, Y. H., Chien, S. C., Hsieh, M. C., Hsiao, P. W., Lee, W. H., Kuo, Y. H., & Yang, N. S. (2016). Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis. Nature Communications, 7, [11311]. https://doi.org/10.1038/ncomms11311